The present invention relates to methods of detecting viable tissue in an organism, and in particular, to such a method that relies upon the capability of viable tissue to utilize an adenosine triphosphate (ATP) repleting agent to synthesize ATP.
There exist specific techniques for determining the viability of biological tissues of different types in an organism. For example, thallium-201 (Tl-201) scintigraphy has been used extensively in the diagnosis of coronary artery disease. Tl-201 scintigraphy is the process of introducing Tl-201 into heart tissue, scanning the heart to detect the radioactive emissions induced by the Tl-201, and using the detected emissions to form images of the heart. A Tl-201 scan image identifies two types of defects, a "persistent defect" and a "transient defect." A persistent defect is defined as a region of heart tissue or myocardium that is deficient Tl-201 activity, and a transient defect is defined as a region of myocardium that is only temporarily deficient of Tl-201 activity.
Tl-201 scintigraphy is typically conducted in two separate studies in conjunction with exercise testing of a patient. Tl-201 is administered by injection into the patient's bloodstream. Tl-201 is administered during the first study at peak exercise during which single images of the heart are obtained in each of several projections. Whenever the images indicate generally uniform Tl-201 activity in all regions of the heart, the heart is considered to be free from defects. Whenever an image indicates a region of no or decrease Tl-201 activity, the heart is considered to have a defect. After a standard redistribution period of about four hours, imaging of the heart is repeated in similar projections. The defect regions of the first scan image are examined to determine whether the defect region "filled-in" with Tl-201 after the redistribution period between the first and second studies. A region that does not fill in with Tl-201 is denominated a persistent defect, which is currently viewed as representing scarred nonviable heart tissue. A region that does fill in with Tl-201 is denominated a transient defect, which is currently viewed as transiently ischemic but viable heart tissue that is "at risk" for infarction.
The interpretation of images developed by Tl-201 scintigraphy has been widely discussed by medical practitioners and researchers. For example, an article by Pohost, Gerald M. et al., "Thallium Redistribution: Mechanisms and Clinial Utility," Seminars in Nuclear Medicine, Vol. X, No. 1, January 1980, pp. 70-93, states that the uptake of Tl-201 is related to regional perfusion of viable heart tissue cells and the capability of the cells to extract the isotope. Pohost et al. conclude that periods of interrupted blood flow to regions of the heart (1) do not irreversibly affect the capability of reversibly damaged heart tissue cells in those regions to extract Tl-201, and (2) leads to a low extraction capability in those regions of irreversibly damaged heart tissue cells. In short, the Pohost et al. article suggests that Tl-201 imaging is clinically useful for distinguishing among noninschemic, ischemic but viable, and permanently injured heart tissue.
The clinical utility of Tl-201 myocardial imaging as advocated by Pohost et al. has, however, been challenged. For example, the abstract by Liu, Peter et al., "Normalization of Persistent Defects on Thallium Scans after Myocardial Revascularization: Scar or Ischemia?", Journal of American College of Cardiology, Vol. 3, No. 2, February 1984, p. 607, reports that a normalization of persistent Tl-201 image defects can occur after angioplasty of severely constricted coronary vessels. (Angioplasty is a "salvage" procedure by which a constriction in a blood vessel is at least partly dilated to increase the flow of blood through it.) Liu et al. recommend that persistent defects should no longer preclude reperfusion procedures in regions where the heart tissue was thought to be irreversibly injured.
In addition, the article by Melin, Jacques A. et al., "Differences in Thallium-201 Uptake in Reperfused and Non reperfused Myocardial Infarction," Circulation Research, Vol. 53, No. 3, September 1983, pp. 414-419, casts doubt on the validity of the assertion that Tl-201 is extracted or taken up only in viable tissue. Melin et al. report that, although there is a close correlation between Tl-201 uptake and regional myocardial blood flow, Tl-201 uptake occurs in reperfused infarcted tissue despite the necrosis thereof. The Tl-201 uptake occurring in reperfused infarcted tissue does so, however, in reduced concentrations relative to blood flow. Melin et al. conclude that their study demonstrates that the presence of Tl-201 uptake is an unreliable indicator of myocardial injury and that reperfused necrotic tissue may have remarkably high levels of Tl-201 uptake.
The article by Braunwald, Eugene et al., "The Stunned Myocardium: Prolonged Post-Ischemic Ventricular Dysfunction," Circulation, Vol. 66, No. 2, December 1982, pp. 1146-1149, proposes that ischemia, i.e., the temporary lack of blood supply to a tissue, is not an "all-or-none" process because recovery of mechanical function, biochemical or metabolic processes, and ultrastructural integrity in viable postischemic myocardial tissue may occur over prolonged periods, which can range from several hours to days. Braunwald et al. suggest that Tl-201 may redistribute very slowly into "sick" or "stunned" tissue from a lack of blood supply to the region. The article by Braunwald et al. suggests that there exists a need to distinguish "stunned" myocardium from permanently injured myocardium in interpreting a Tl-201 persistent defect image.